High molecular weight transforming growth factor (TGF) activities can be detected in the urine of patients with a variety of disseminated cancers. These acid- and heat-stable polypeptides compete for binding to epidermal growth factor (EGF) membrane receptors and promote the anchorage-independent growth of nontransformed cells. This high molecular weight TGF activity (30,000-35,000 Mr), which coelutes with EGF-competing activity, was found in the urine of 18 of 22 cancer patients with diagnoses including carcinoma of the lung, breast and colon, as well as sarcomas and melanomas. Low, but detectable, amounts of this TGF activity were found in only 5 of 30 nonmalignant controls which included both normal individuals and patients with a variety of inflammatory disorders. This high molecular weight TGF differs from EGF in apparent molecular weight, soft agar growth-stimulating activity and high pressure liquid chromatography elution profile. These findings suggest that urine may provide a convenient source for the biochemical characterization of these TFG-like activities which may be clinically useful biological markers of certain types of cancer.